三阴性乳腺癌是一类雌激素受体、孕激素受体、表皮生长因子受体-2均为阴性表达的乳腺癌亚型。雌孕激素与三阴性乳腺癌的发生密切相关，但其作用机制尚不明确。前期研究工作显示，雌孕激素联合给药可下调三阴性乳腺癌细胞中miR-145的表达，并诱导三阴性乳腺癌的发生。本研究拟利用TA2小鼠这一理想肿瘤模型，明确雌孕激素在三阴性乳腺癌发生过程中的作用，观察雌孕激素和miR-145表达水平间的相关性，阐述雌孕激素对miR-145及其靶基因IGF-1R的调控作用，探讨雌孕激素影响三阴性乳腺癌发生的相关分子机制，为miR-145作为三阴性乳腺癌的早期诊断和靶向治疗指标提供实验基础和理论依据。

Triple-negative breast cancer (TNBC) is an subtype of breast cancer with absent expression of estrogen receptor, progesterone receptor, and HER-2. Estradiol and progesterone play important roles in the incidence of TNBC. However, the mechanism of regulating tumorigenesis are still to be elucidated. Our previously results showed that combined treatment with estradiol and progesterone inhibited the expression of miR-145 in TNBC cells, and increased the incidence of TNBC. Using TA2 mice TNBC model, our study will identify the roles of estradiol and progesterone in the incidence of TNBC, observe the relationgship between the level of estradiol / progesterone and miR-145, discuss the effect of estradiol and progesterone in regulating miR-145 and its target gene IGF-1R, and investigate the molecular mechanism of estradiol and progesterone in inducing TNBC. The study will provide evidence for miR-145 used as biomarkers for early dygnosis and targeted therapy of TNBC..